Alzheimer’s drug may reduce urge to eat compulsively

February 19, 2015

Binge-eating disorder affects nearly 10 million American adults, by some estimates. It’s a vicious condition in which people repeatedly eat huge amounts of food—often high-calorie sweets and/or fatty snacks—in a couple of hours or less. Perhaps the worst part of the disorder is that each binge leads to feelings of embarrassment, self-disgust, and depression.

“The disorder resembles addiction more than any other eating disorder. Binge eaters understand the consequences of their behavior, but they can’t stop. It’s a compulsion,” says senior author Pietro Cottone, a MED associate professor of pharmacology and psychiatry and codirector of the Laboratory of Addictive Disorders.

Cottone, who has been studying addiction for over a decade, says that binge eating triggers patterns of chemical responses in the brain that are similar to those in drug and alcohol addiction. In all these disorders, he says, a region called the nucleus accumbens, which provides a communication link between the emotional and reasoning centers of the brain, is particularly important because of its role in eliciting and modulating behavior.

“When you eat, have sex, do drugs—all that stuff—this area gets activated,” says Cottone. During binge-eating episodes, the nucleus accumbens does not function properly. That’s where the Alzheimer’s drug memantine comes in.

Memantine blocks receptors in the brain that bond with glutamate, a neurotransmitter known to stimulate neurons. In Alzheimer’s disease, dying brain cells release excess glutamate, which overstimulates healthy cells and can kill them. So by blocking glutamate receptors, memantine protects healthy cells in the Alzheimer’s brain. Cottone suspected that the drug, by blocking glutamate receptors, could also curb binge eating. With glutamate locked out, he believed the nucleus accumbens wouldn’t reinforce the stimuli associated with junk food so much, and the urge to binge eat should fade.

Cottone tested the hypothesis with two groups of rats. One group was fed a diet of regular rat food. The others also got regular food, but for one hour a day they were also offered junk food, which contained an extra dose of sugar. It was the rat equivalent of jelly beans and gumdrops, and “they loved it,” says Cottone.

Within days, the junk food rats started bingeing. “We made them into binge eaters just by giving them access for one hour,” he says. “It was insane.” And even worse: the more the rats binged on junk food, the less they ate the regular food. “Exactly what happens in people, we did with rats,” he says.

Cottone wondered if the binge-eating rats would take more risks to reach their junk food. He put the rats into a box that was half dark and half brightly lit. Rats are nocturnal and will usually do anything to avoid bright light: when he put a bowl of junk food in the middle of the bright box, the regular-chow rats wouldn’t touch it. “They don’t even think about eating the food,” he says. “They were like, no way!” But the binge eaters couldn’t stop themselves—they ran into the light, stuck their snouts into the junky kibble, and gobbled it up. “This is a lapse of judgment,” says Cottone, noting that such behavior is a hallmark of addiction. “They know the environment is potentially dangerous, but they go there anyway.”

All this changed when memantine entered the mix. The scientists injected the drug into both groups of rats. In the regular-chow rats, it had no effect. But for the binge eaters, the changes were profound. Not only did their binge eating decrease dramatically, but they were no longer willing to take risks to get their junk food. The scientists found the same effect when they injected memantine directly into the shell of the nucleus accumbens.

Cottone and his team hope that memantine may prove a useful treatment for binge-eating disorder, for which there are currently no Food and Drug Administration–approved drugs. “Individuals with binge-eating disorder have a very poor quality of life. Our study gives a better understanding of the underpinning neurobiological mechanisms of the disorder,” says article coauthor Valentina Sabino, a MED assistant professor of pharmacology and psychiatry and codirector of the Laboratory of Addictive Disorders.

Although one small 2008 study in the International Journal of Eating Disorders found that memantine may be useful for treating binge eating in humans, there has been little additional research in this area. “We hope that this paper will help revitalize this line of research,” says Cottone, who anticipates seeing larger, more robust human trials in the future. “We need more pharmacological approaches.”